Compound | Simulation Method | Cmax | tmax | AUC0–∞ | t1/2 |
---|---|---|---|---|---|
μg/ml | h | μg · h/ml | h | ||
PF02341066 | OBS | 0.061 | 2.5 | 0.60 | 10 |
ALS-total | 0.067 (1.1) | 6.0 (2.4) | 2.2 (3.7) | 18 (1.8) | |
ALS-free | 0.034 (1.8) | 5.8 (2.3) | 1.1 (1.8) | 17 (1.6) | |
PBPK-IVIVE | 0.16 (2.6) | 1.7 (1.5) | 1.1 (1.9) | 12 (1.2) | |
PBPK-ALS | 0.081 (1.3) | 1.6 (1.6) | 0.48 (1.2) | 12 (1.1) | |
PF04217903 | OBS | 0.24 | 1.2 | 0.81 | 6.6 |
ALS-total | 0.060 (4.0) | 2.1 (1.8) | 0.44 (1.8) | 3.2 (2.0) | |
ALS-free | 0.31 (1.3) | 1.7 (1.5) | 1.6 (1.9) | 1.9 (3.4) | |
PBPK-IVIVE | 0.17 (1.4) | 0.9 (1.3) | 1.8 (2.2) | 11 (1.7) | |
PBPK-ALS | 0.10 (2.3) | 0.8 (1.5) | 0.64 (1.3) | 6.3 (1.0) |
OBS, observed mean PK parameters; ALS-total, simulated PK parameters by allometric scaling for CLblood and Vss; ALS-free, simulated PK parameters by allometric scaling for CLint and Vss,| u; PBPK-IVIVE, simulated PK parameters by PBPK modeling using hepatic CL predicted from IVIVE (WS-II); PBPK-ALS, simulated PK parameters by PBPK modeling using hepatic CL predicted from allometric scaling for CLint.